The Competition Between Splicing and 3′ Processing Shapes the Human Transcriptome

Authors

• Lindsey V. Soles, University of California, Irvine
• Shuangyu Li, University of California, Irvine
• Liang Liu, University of California, Irvine
• Kristianna S.K. Sarkan, Chapman UniversityFollow
• Erik G. Alvstad, University of California, Irvine
• Lusong Tian, University of California, Irvine
• Yoseop Yoon, University of California, Irvine
• Marielle Valdez, University of California, Irvine
• Ivan Marazzi, University of California, Irvine
• Yongsheng Shi, University of California, Irvine

Document Type

Article

Publication Date

5-15-2026

Abstract

Eukaryotic pre-mRNA processing steps, including splicing and 3′ processing, are tightly coordinated, yet the underlying mechanisms remain incompletely understood. U1 snRNP has been proposed to inhibit 3′ processing at intronic polyadenylation (IPA) sites through a splicing-independent mechanism termed telescripting. In contrast, we discovered that disrupting splicing by using six different methods—targeting various key components such as U1 snRNP, U2 snRNP, U2AF, and SF3b—activates 3′ processing at thousands of IPA sites. Notably, splicing inhibition, especially of U1 snRNP, induced widespread premature transcription termination within gene bodies through both IPA-coupled and IPA-independent mechanisms. Inhibition of different splicing factors activated overlapping and distinct sets of IPA sites, reflecting their specific contributions to transcription and spliceosome function. Conversely, inhibition of 3′ processing enhanced splicing globally. These findings support a model in which splicing and 3′ processing are competing processes that intersect with transcription to shape the transcriptome landscape.

Comments

This article was originally published in Genes & Development, volume 40, in 2026. https://doi.org/10.1101/gad.353718.126

Recommended Citation

Soles LV, Li S, Liu L, Sarkan KSK, Alvstad EG, Tian L, Yoon Y, Valdez M, Marazzi I, Shi Y. 2026. The competition between splicing and 3′ processing shapes the human transcriptome. Genes & Dev. 40: 1099-1118. https://doi.org/10.1101/gad.353718.126

Copyright

The authors

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License